Effect of grinding on dehydration of crystal water of theophylline.
The effect of grinding on the dehydration of crystal water of theophylline has been studied. It was observed that the water content of theophylline hydrate decreased with increased grinding time. As the grinding time proceeded, the results of differential scanning calorimetry (DSC) indicated that crystal water of ground theophylline hydrate dehydrated in three steps at ca. 58, 44, and 17 degrees C, respectively. Powder X-ray diffraction study revealed that the crystal lattice of theophylline monohydrate collapsed by grinding, and part of the theophylline molecules subsequently rearranged the collapsed lattice to form theophylline anhydrate. The result of Fourier transformed infrared spectroscopy demonstrated that the hydrogen bonds between crystal water molecules and theophylline molecules were weakened or destroyed to some extent by grinding. It was supposed that crystal water in the ground theophylline hydrate might exist at least in three molecular states of different hydrogen-bonding. From DSC study, it was suggested that the ruptured hydrogen bonds of water molecules in the ground theophylline hydrate were strengthened after storage under 96.5% relative humidity at 30 degrees C.
Puttipipatkhachorn
S
S
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Yonemochi
E
E
Oguchi
T
T
Yamamoto
K
K
Nakai
Y
Y
D002152:Calorimetry, Differential Scanning; D003890:Desiccation; D004339:Drug Compounding; D005583:Fourier Analysis; D013055:Spectrophotometry, Infrared; D013806:Theophylline / Q000737:chemistry*; D014961:X-Ray Diffraction
D013806:Theophylline